Infant Formula Milk Research Articles

Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle Material.

Human milk serves the sole nutritional role for the developing infant. During lactation, nano-sized extracellular vesicles (EVs) in milk containing a multitude of biologically active components are transferred from mother to offspring. Infant formula (IF) based on cow milk-derived ingredients has been reported to contain reduced levels of EVs as compared to human milk. There is therefore an unmet need to produce large-scale volumes of milk EVs to improve IF composition. Here, we report a scalable industrial production protocol for a bovine whey-derived ingredient that is highly enriched in EV material using a large-scale sequential ceramic membrane filtration setup. Furthermore, we demonstrate a robust and generally applicable analytical approach to determine the relative contributions of EVs and milk fat globule membrane (MFGM) using molar ratios of the membrane-bound proteins butyrophilin (BTN) and CD9 as surrogate markers for MFGM and EVs, respectively. Taken together, our findings provide a basis for comparing bovine milk-containing foods and aid in developing specialized ingredients that can minimize the compositional difference between infant formula and human milk.

Safety assessment of the substance N,N'-(2-(4-(2-aminobenzamido)butyl)pentane-1,5-diyl)bis(2-aminobenzamide) for use in plastic food contact materials.

The EFSA Panel on Food Contact Materials assessed the safety of N,N'-(2-(4-(2-aminobenzamido)butyl)pentane-1,5-diyl)bis(2-aminobenzamide) to be used at up to 650 mg/kg in polyethylene terephthalate (PET) to scavenge acetaldehyde (AA). Final articles are intended for contact with aqueous, acidic and low-alcoholic beverages for long-term storage at room temperature and below. The migration of the substance from PET bottles into 20% ethanol was 0.0038 mg/kg food. The Panel calculated the potential migration of the summed reaction products not to exceed 0.02 mg/kg food. From experimental studies, the Panel excluded genotoxicity concerns for the substance, for 2-aminobenzamide +1 formaldehyde and 2-aminobenzamide +1 AA, both with desaturation. In silico predictions, previous EFSA evaluations and the use of the threshold of toxicological concern (TTC) excluded genotoxicity concerns for 15 other impurities/reaction products. A tentatively identified by-product was predicted as possible DNA-reactive invitro mutagen and clastogen, due to its aromatic hydroxylamine group. Its modelled migration would not exceed 0.14 μg/kg food, leading to a potential exposure below the TTC of 0.0025 μg/kg body weight per day. Non-identified reaction products are expected to be structurally related to the identified ones and, hence, not to raise concern for genotoxicity. The Panel concluded that the substance is not of safety concern for the consumer, if it is used as an additive at up to 650 mg/kg in PET intended for contact with foods simulated by simulants A, B and C, for storage above 6 months at room temperature and below, including hot-fill conditions and/or heating up to 70°C ≤ T ≤ 100°C for maximum t = 120/2((T-70)/10) minutes. The substance should not be used for infant formula (including water used for reconstitution) and human milk. The migration of the substance should not exceed 0.05 mg/kg food. The substance should not contain aromatic hydroxylamine derivatives at more than 0.15% w/w.

ORIGINS: Nutritional Profile of Children Aged One Year in a Longitudinal Birth Cohort.

Dietary intake during the first year of life is a key determinant of a child's growth and development. ORIGINS is a longitudinal birth cohort study investigating factors that contribute to a 'healthy start to life' and the prevention of non-communicable diseases. This descriptive cross-sectional study aims to describe the dietary intakes of one-year-old children participating in ORIGINS and compare these to the Australian Dietary Guidelines and Nutrient Reference Values (NRVs). Between 2020 and 2023, dietary intake data were collected on 779 one-year-old children using a Food Frequency Questionnaire (FFQ). The analysis explored milk intake (breastmilk, infant formula, and cow's milk), the introduction to solids, macronutrient, micronutrient, and food group intakes. The results indicated that 41.5% were still being breastfed at one year of age, while 58.0% continued to receive formula milk. While the cohort met NRV cut-offs for most micronutrients, iodine intake fell below requirements, and sodium intake exceeded recommendations. Diet quality, based on the food group intake, did not meet recommendations, with children over-consuming fruit and discretionary foods, while under-consuming vegetables and cereals and grains foods. These findings highlight areas for improvement in the dietary intake of one-year-old children.

Three Years of Human Milk Banking: Assessing the Impact on Lactation Rates at Discharge in VLBW Preterm Infants in an Italian Reference NICU.

Background: Human milk (HM) offers critical short- and long-term benefits for preterm and very low birth weight (VLBW) infants. In 2021, a human milk bank (HMB) was established at the IRCCS Giannina Gaslini Institute, aiming to improve HM feeding rates in this vulnerable population. Methods: We retrospectively analyzed feeding data from 442 VLBW infants (BW < 1500 g) admitted between 2018 and 2024. Data were drawn from the Vermont Oxford Network and Italian Neonatal Network registries. Feeding modalities-exclusive HM, infant formula milk (IM), and mixed feeding (MF)-were recorded and analyzed before and after HMB introduction. Results: Before 2021, MF was predominant, with exclusive HM rates below 10%. Following HMB implementation, exclusive HM feeding increased significantly, reaching 47.2% in 2024 (p < 0.0001). Regression analysis showed a positive trend for HM (+4.84%/year, p = 0.05), and a declining trend for IM (-1.96%/year) and MF (-2.88%/year). Projections suggest HM rates may exceed 58% by 2030. Conclusions: The introduction of the HMB was associated with a significant shift in feeding practices, increasing HM use and reducing IM exposure among VLBW infants. These findings underscore the importance of institutional strategies such as donor milk availability, lactation support, and maternal education in optimizing neonatal nutrition. Ongoing efforts are essential to sustain and extend these improvements beyond NICU discharge, ensuring the long-term benefits of human milk for preterm infants.

Enhanced brain myelination and cognitive development in young children associated with milk fat globule membrane (MFGM) intake: a temporal cohort study.

Myelination is an important neurodevelopmental process that facilitates efficient brain messaging and connectivity, and contributes to the emergence and refinement of cognitive skills and abilities. Healthy maturation of the myelinated white matter requires coordinated delivery of key nutritional building blocks, including short and long-chain polyunsaturated fatty acids, phospholipids, and sphingolipids. While many of these nutrients are amply supplied by breastmilk, they may not be present in sufficient quantity in infant formula milk. Milk fat globule membrane (MFGM) is a rich source of phospholipids, including sphingomyelin and has been associated with improved cognitive development in infants and children when added to infant formula. To determine if added bovine MFGM is also associated with improved myelination, this study used myelin-sensitive MRI to compare myelination trends in healthy infants and toddlers, 0-2years of age, who received the same branded infant formula with and without added bovine MFGM in two temporal cohorts: Without Added MFGM between 2010 and 2017; and With Added MFGM between 2018-2020. Concurrent with imaging, cognitive development was assessed using the Mullen Scales of Early Learning (MSEL). Matched for important demographic and socioeconomic characteristics, we found that children who received infant formula with added MFGM showed improved myelination in motor-related areas (motor cortices, internal capsule, and cerebellum) and improved MSEL gross and fine motor scores. No significant differences in verbal or overall cognitive ability scores were noted. These results support the importance of phospholipids, sphingolipids, and sphingomyelin in promoting brain myelination and cognitive development.

History of the creation of infant milk formula

Adequate nutrition during the first months of life is essential for newborns and infants to ensure their growth and development. If women are unable to breastfeed for medical or social reasons, milk formulas become the primary source of nutrition for infants. Modern infant milk formulas are developed with due account for the latest discoveries in science regarding the growing body needs and include various functional components that contribute to a baby’s healthy growth and development. However, the histories of creation and evolution of milk formulas are always interesting. The article describes how different nations approached the issues of feeding babies using alternatives to the breast milk, including goat’s and cow’s milk, as well as plant-based formulas. Special attention is paid to the research discoveries in the field of nutrition and medicine that inspired the creation of safe nutritional formulas. Currently, rapid technological advancements can provide modern formula-fed infants with oligosaccharides with structures identical to human milk oligosaccharides, polyunsaturated fatty acids (omega-3 and omega-6) such as docosahexaenoic acid (DHA) and arachidonic acid (ARA) and other useful components. New infant formulas for artificial and/or mixed feeding from birth stand out particularly. Their composition meets all the requirements for the production of infant formula and is enriched with a combination of 2′-fucosylated oligosaccharides (2′-FL) and galacto-oligosaccharides (GOS), which can give a long-range outlook for the use of infant formulas.

Life cycle assessment of a semi-industrial infant milk formula powder and of a low-heat alternative process involving membrane filtration

Life cycle assessment of a semi-industrial infant milk formula powder and of a low-heat alternative process involving membrane filtration

A Hazard Does Not Always Equate to a Risk: Cronobacter is a rare opportunistic pathogen and the greatest risk is only for a small sub-population of infants and only associated with powdered infant formula or human breast milk

A Hazard Does Not Always Equate to a Risk: Cronobacter is a rare opportunistic pathogen and the greatest risk is only for a small sub-population of infants and only associated with powdered infant formula or human breast milk

Simulated gastrointestinal protein digestion of sheep and goat milk infant formulae

Simulated gastrointestinal protein digestion of sheep and goat milk infant formulae

Relevance of Milk Composition to Human Longitudinal Growth from Infancy Through Puberty: Facts and Controversies.

Milk is the principal nutrient of newborn humans and a diagnostic feature of the order Mammalia. Its release is elicited as a reflex by infant sucking under the control of the hormone oxytocin. While it is recognized that breast milk optimally promotes infant longitudinal growth and development, this review explores facts and controversies regarding the extent to which the milks of several dairy animals and infant formula milk (IF) approximate special properties and bioactivities of breast milk. It also provides evidence that early exposure to undernutrition during the very rapid fetal and early infancy growth predominantly and permanently stunts longitudinal growth trajectory in both animals and humans and is often followed in later life by obesity and metabolic dysfunction, and sometimes also by precocious timing of sexual maturation. There is a knowledge gap as to whether there may be additional critical periods of nutritional vulnerability in human development, which is characterized by a relatively prolonged period of slow childhood growth bracketed by the rapid fetal-neonatal and pubertal growth spurts. It is also unclear whether any quantitative differences in caloric intake and supply during neonatal period may influence developmental fatness programming. A further knowledge gap exists regarding the role of infant microbiome composition and development in the possible epigenetic programming of longitudinal growth or fatness in later life. Extending the research of early developmental programming to the entire period of human growth from conception to the end of puberty, examining infant caloric intake and supply as possible factors modulating the epigenetic programming in favor of obesity, and examining the role of infant gut microbiome in developing infant's capacity to process nutrients may provide a better understanding of the interaction between critical nutritional influences in the control of human longitudinal growth and later-life obesity.

Application Progress of Immobilized Enzymes in the Catalytic Synthesis of 1,3-Dioleoyl-2-palmitoyltriglyceride Structured Lipids.

In recent years, the preparation of OPO (1,3-dioleoyl-2-palmitoyltriglyceride)-structured lipids through immobilized lipase catalysis has emerged as a research hotspot in the fields of food and biomedical sciences. OPO structured lipids, renowned for their unique molecular structure and biological functions, find wide applications in infant formula milk powder, functional foods, and nutritional supplements. Lipase-catalyzed reactions, known for their efficiency, high selectivity, and mild conditions, are ideal for the synthesis of OPO structured lipids. Immobilized lipases not only address the issues of poor stability and difficult recovery of free enzymes but also enhance catalytic efficiency and reaction controllability. This review summarizes the latest advancements in the synthesis of OPO structured lipids using immobilized lipases, focusing on immobilization methods, enhancements in enzyme activity and stability, the optimization of reaction conditions, and improvements in product purity and yield. Furthermore, it delves into the reaction mechanisms of enzymatic synthesis of OPO structured lipids, process optimization strategies, and the challenges and broad prospects faced during industrial applications.

Investigation of aflatoxin M1 in infant formula and raw milk in northwestern Syria.

Investigation of aflatoxin M1 in infant formula and raw milk in northwestern Syria.

A Time-Resolved Fluorescent Microsphere Immunochromatographic Assay for Determination of Vitamin B12 in Infant Formula Milk Powder.

Vitamin B12 (VB12) is an important nutrient, and its quality control in food is crucial. In this study, based on the principle of specific recognition of target analyte by monoclonal antibodies (mAbs), a time-resolved fluorescent microsphere immunochromatographic assay (TRFM-ICA) was developed to detect the content of VB12 in infant formula milk powder. First, the performance of the anti-VB12 mAb was evaluated, revealing a half-maximal inhibitory concentration of 0.370 ng/mL, an affinity constant of 2.604 × 109 L/mol and no cross-reactivity with other vitamins. Then, a highly sensitive TRFM-ICA was developed, with a visual limit of detection of 10 μg/kg and a cut-off value of 100 μg/kg for qualitative detection and a detection range of 4.125-82.397 μg/kg for quantitative detection. In addition, the test results of real samples were consistent with the results of quantification using microbiological methods, with a coefficient of variation of less than 10%, showing good accuracy and stability, and confirming that the TRFM-ICA is suitable for the analysis of VB12 in real infant formula milk powder samples. In this study, based on the principle of specific recognition of VB12 by monoclonal antibodies (mAbs) against VB12, a time-resolved fluorescence microsphere immunochromatographic assay (TRFM-ICA) was developed to detect the content of VB12 in infant formula by converting biological signals into optical signals.

Maternal exposure to purified versus grain-based diet during early lactation in mice affects offspring growth and reduces responsivity to Western-style diet challenge in adulthood.

The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed "nutritional programming." Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.

Gastrointestinal Health and Immunity of Milk Formula Supplemented with a Prebiotic Mixture of Short-Chain Galacto-oligosaccharides and Long-Chain Fructo-Oligosaccharides (9:1) in Healthy Infants and Toddlers: A Systematic Review with Meta-Analysis.

Prebiotics are substrates selectively utilized by microorganisms to confer health benefits to their hosts. Various prebiotics have been supplemented in standard milk formulas for infants who cannot be exclusively breastfed, aiming to provide benefits similar to those of breast milk. One of the most commonly used prebiotics is a mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS [9:1]). Systematic review and meta-analysis were conducted to determine the effectiveness of scGOS:lcFOS (9:1) supplementation in standard milk formula for improving gastrointestinal health and immunity among healthy infants and toddlers, using parameters such as stool pH and intestinal colonization with beneficial bacteria. This systematic review was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Randomized clinical trials comparing scGOS/lcFOS (9:1)-supplemented formula versus placebo- or non-supplemented formula milk were eligible for inclusion. Related studies on gastrointestinal health and immunity among healthy infants up to five years old were searched from the earliest available date until February 29, 2024. Eighteen publications (number of participants=1,675) were selected for the systematic review, of which 11 were subsequently subjected to a meta-analysis. Results showed that the standard formula supplemented with scGOS/lcFOS (9:1) was well tolerated and conferred various gastrointestinal health and immunity to healthy infants and toddlers. These findings support the supplementation of standard milk formula with scGOS/lcFOS (9:1) for healthy infants and toddlers.

Lipidomic study of yak milk reveals potential biomarkers for the design of infant formulas.

Lipidomic study of yak milk reveals potential biomarkers for the design of infant formulas.

Detection and exposure risk assessment of chloropropanol ester and glycidyl ester in infant formula milk powder

To investigate the contamination level of chloropropanols esters(MCPDEs) and glycidyl esters(GEs) in infant milk powder, and to assess the risk of exposure to MCPDEs and GEs in infant formula milk powder in Hangzhou. Non-derivatization gas chromatography-tandem mass spectrometry(GC-MS/MS) was used to detect MCPDEs in 73 samples of commercially available infant milk powder, including 3-chlorine-1, 2-propylene glycol ester, 3-MCPDE), 2-monochloropropane-1, 3 diol esters(2-MCPDE) and GEs. Dietary exposure assessment of chloropropanols esters and glycidyl esters were evaluated by evaluation method and margin of exposure(MOE) respectively. The detection rates of 3-MCPDE, 2-MCPDE and GEs were 100.0%, 82.2% and 78.1%. The average detection concentrations were 0.051, 0.015 and 0.018 mg/kg, respectively. The average and P95 dietary exposure values for 3-MCPDE were 0.48-1.41 and 0.81-2.69 μg/(kg·BW·d). For GEs, these were 24 669-58 945 and 10 881-21 540 respectively. The median exposure value of 3-MCPDE in infant milk powder is less than the TDI, and the health risk is small. But the P95 value of 3-MCPDE for infant aged 0-6 months is 2.69 μg/(kg·BW·d), greater than TDI value, so high health risk exists. The MOE for infants aged 0-6 months is lower than 25 000, and it may pose a potential risk. The MOE for children aged 6-36 months is higher than 25 000, and the health risk is very low.

Dairy Foods: A Matrix for Human Health and Precision Nutrition-Effect of processing infant milk formula on protein digestion and gut barrier health (in vitro and preclinical).

Dairy Foods: A Matrix for Human Health and Precision Nutrition-Effect of processing infant milk formula on protein digestion and gut barrier health (in vitro and preclinical).

Safety assessment of the substance 2,2'-oxydiethylamine for use in plastic food contact materials.

The EFSA Panel on Food Contact Materials assessed the safety of 2,2'-oxydiethylamine, which is intended to be used at up to 14% w/w as a monomer along with adipic acid and caprolactam to make polyamide thin films intended for single use, in contact with all types of food under all conditions of time and temperature. Specific migration of 2,2'-oxydiethylamine was tested from a polyamide film in water and was below the limit of quantification (LOQ) of 0.015 mg/kg. Migration of impurities has been estimated pro-rata. Migrating oligomers were identified and semi-quantified in 10% ethanol, 3% acetic acid and olive oil. Considering the measured migration and the virtual presence at the LOQ of the oligomers below 1000 Da containing the substance, the estimated migration of these oligomers would be 1.042 mg/kg. Genotoxicity studies were performed on the substance and on 1-oxa-4,11,18-triazacycloeicosane-5,10,17-trione and 1-oxa-4,11,18,25-tetraazacycloheptacosane-5,10,17,24-tetraone. (Q)SAR analyses were provided on the oligomers of higher molecular masses. Based on these data, the Panel excluded genotoxicity concerns for the substance and its oligomers. From a 90-day toxicity study on the 1-oxa-4,11,18-triazacycloeicosane-5,10,17-trione, the Panel identified a NOAEL of 1040 mg/kg bw per day. Based on their physico-chemical properties and experimental data, the Panel considered the potential for accumulation in humans of the oligomers containing the substance of no concern. The Panel concluded that the substance is not of safety concern for the consumer if it is used as a comonomer with 99.6% minimum purity at up to 14% w/w to manufacture polyamide films (maximum thickness: 25 μm) and intended to be used in contact with all types of foods, except infant formula and human milk, at all time and temperature conditions. The migrations of the substance and of the oligomers below 1000 Da containing the substance should not exceed 0.05 and 5 mg/kg food, respectively.

An investigation into the parental attitudes and challenges faced when introducing solid foods to infants in Ireland

The introduction of complementary foods, also known as 'weaning', refers to the process of introducing solid foods into an infant’s diet, alongside breast milk or infant formula milk(1). According to the Food Safety Authority of Ireland (FSAI) guidelines, weaning should commence around 6 months of age, with no earlier or later than 17 or 26 weeks, respectively(2). These guidelines provide evidence-based recommendations aimed at promoting optimal infant health, growth, and development(3). The aim of this study was to gain an insight into parental attitudes towards weaning and the common challenges faced when introducing solids.Data was collected using a 16-item questionnaire. Parents of infants aged 0–12 months were recruited through an online parenting club and descriptive statistics were performed using IBM SPSS (V29) to determine percentages.Of the 215 participants, 64% (n = 137) had initiated solid food introduction to their infants, with the age of these infants ranging from 4-12 months. Of those, the majority (80%, n = 109) followed FSAI guidelines(2), introducing new foods daily or every few days. The main factors guiding this decision were signs of readiness and developmental milestones, cited by 76% of respondents (n = 104). Among those who began weaning (n = 137), 70% reported a positive experience, though the majority (92%, n = 126) encountered challenges along the way. These included infant’s refusal to eat (34%, n = 47), allergy concerns (41%, n = 56), and difficulty determining appropriate portion sizes (48%, n = 66). Our findings showed that 12% (n = 16) of infants aged 6-9 months and 2% (n = 3) of infants aged 10-12 months had not yet been introduced to meat, poultry, or fish. Additionally, 4% of parents (n = 6) waited until their infants were at least 9 months old to introduce these foods, despite guidelines recommending early exposure to iron-rich foods(2).Most parents with infants aged 0-6 months (64%, n = 78) had not started weaning. Among them, 26% (n = 20) felt very confident about beginning the process, while 25% (n = 19) lacked confidence in introducing solid foods to their infants.Among all participants, information on weaning commonly came from family/friends (68%, n = 147), healthcare professionals (60%, n = 128), and social media (46%, n = 99). When asked about resources they would like access to, nearly two-thirds of parents (64%, n = 138) expressed interest in weaning recipe ideas. Additionally, 53% (n = 114) highlighted the need for guidelines on the appropriate amount of milk to give during weaning.In conclusion, our findings indicate that while most parents appear compliant with the recommended timing of weaning, challenges still persist. Moreover, there is a notable reliance on various sources for weaning information, with a demand for resources like weaning recipes and milk quantity guidelines. These insights highlight the importance of tailored support and education to facilitate a positive weaning experience for both parents and infants.